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Enhancing The Anti-tumor Effect Of Melphalan By Prior Administration Of L-amino Acid Oxidase With Or Without Intermediate Administration Of Anti-L-amino Acid Oxidase Antibody - Patent 5523084

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Both embodiments of the invention herein are directed at the use of melphalan as an anti-tumor agent.BACKGROUND OF THE INVENTIONMelphalan, (4-[bis(2-chloroethyl)amino]-L-phenylalanine), is a nitrogen mustard that is useful as a chemotherapeutic agent. Goodman and Gilman's The Pharmaceutical Basis of Therapeutics, 8th edition, pages 1202-1208 (1990) classifies melphalanas an alkylating agent type of chemotherapeutic action and indicates a mechanism of action of cross-linking DNA. Sarosy, G., et al, Journal of Clinical Oncology, Vol. 6, No. 11 (November), pp. 1768-1782 (1988) indicates that melphalan effectscytotoxicity by forming either interstrand, intrastrand, or DNA-protein cross links.The wide spectrum of melphalan's anti-neoplastic activity against tumors, in vivo, is reported in the literature. Goodman and Gilman's The Pharmaceutical Basis of Therapeutics, 8th edition, pages 1202-1208 (1990) indicates that melphalan iscurrently used in the treatment of multiple myeloma, breast cancer and ovarian cancer. Sarosy, G., et al, Journal of Clinical Oncology, Vol. 6, No. 11 (November), pp. 1768-1782 (1988), a review article on intravenous melphalan usage, at page 1772 inTable 1 indicates that at lower doses intravenous melphalan demonstrated at least some activity against pancreatic cancer, colon carcinoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, and ovarian cancer; at page 1774 in Table 3 indicates that athigher dosages intravenous melphalan demonstrated at least some activity against breast cancer, non-small-cell lung cancer, small-cell lung cancer, colon cancer, melanoma, testicular cancer, ovarian cancer, soft tissue sarcoma, Ewing's sarcoma, synovialcell sarcoma, bone (giant cell) sarcoma, Wilms' sarcoma, Wilms' osteogenic sarcoma, rhabdomyosarcoma, multiple myeloma, neuroblastoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphocytic leukemia, acute nonlymphoblastic leukemia, chronicgranulocytic leukemia and renal cancer and characterizes t

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